Intracellular iron uptake is favored in Hfe-KO mouse primary chondrocytes mimicking an osteoarthritis-related phenotype

HFE-hemochromatosis is a disease characterized by a systemic iron overload phenotype mainly associated with mutations in the HFE protein (HFE) gene. Osteoarthritis (OA) has been reported as one of the most prevalent complications in HFE-hemochromatosis patients, but the mechanisms associated with its onset and progression remain incompletely understood. In this study, we have characterized the response to high iron concentrations of a primary culture of articular chondrocytes isolated from newborn Hfe-KO mice and compared the results with that of a similar experiment developed in cells from C57BL/6 wild-type (wt) mice. Our data provide evidence that both wt- and Hfe-KO-derived chondrocytes, when exposed to 50 mu M iron, develop characteristics of an OA-related phenotype, such as an increased expression of metalloproteases, a decreased extracellular matrix production, and a lower expression level of aggrecan. In addition, Hfe-KO cells also showed an increased expression of iron metabolism markers and MMP3, indicating an increased susceptibility to intracellular iron accumulation and higher levels of chondrocyte catabolism. Accordingly, upon treatment with 50 mu M iron, these chondrocytes were found to preferentially differentiate toward hypertrophy with increased expression of collagen I and transferrin and downregulation of SRY (sex-determining region Y)-box containing gene 9 (Sox9). In conclusion, high iron exposure can compromise chondrocyte metabolism, which, when simultaneously affected by an Hfe loss of function, appears to be more susceptible to the establishment of an OA-related phenotype.European Regional Development FundEuropean Union (EU) [EMBRC.PT Alg-01-0145-FEDER-022121, Norte-01-0145-FEDER-000012]Fundacao para a Ciencia e a TecnologiaPortuguese Foundation for Science and Technology [SFRH/BD/77056/2011]Portuguese Foundation for Science and TechnologyPortuguese Foundation for Science and TechnologyPortuguese Science and Technology FoundationPortuguese Foundation for Science and Technologyinfo:eu-repo/semantics/publishedVersio

ROS/oxidative stress signaling in osteoarthritis

Osteoarthritis is the most common joint disorder with increasing prevalence due to aging of the population. Its multi-factorial etiology includes oxidative stress and the overproduction of reactive oxygen species, which regulate intracellular signaling processes, chondrocyte senescence and apoptosis, extracellular matrix synthesis and degradation along with synovial inflammation and dysfunction of the subchondral bone. As disease-modifying drugs for osteoarthritis are rare, targeting the complex oxidative stress signaling pathways would offer a valuable perspective for exploration of potential therapeutic strategies in the treatment of this devastating disease. © 2016 Elsevier B.V

Redox and NF-κB signaling in osteoarthritis

Human cells have to deal with the constant production of reactive oxygen species (ROS). Although ROS overproduction might be harmful to cell biology, there are plenty of data showing that moderate levels of ROS control gene expression by maintaining redox signaling. Osteoarthritis (OA) is the most common joint disorder with a multi-factorial etiology including overproduction of ROS. ROS overproduction in OA modifies intracellular signaling, chondrocyte life cycle, metabolism of cartilage matrix and contributes to synovial inflammation and dysfunction of the subchondral bone. In arthritic tissues, the NF-κB signaling pathway can be activated by pro-inflammatory cytokines, mechanical stress, and extracellular matrix degradation products. This activation results in regulation of expression of many cytokines, inflammatory mediators, transcription factors, and several matrix-degrading enzymes. Overall, NF-κB signaling affects cartilage matrix remodeling, chondrocyte apoptosis, synovial inflammation, and has indirect stimulatory effects on downstream regulators of terminal chondrocyte differentiation. Interaction between redox signaling and NF-κB transcription factors seems to play a distinctive role in OA pathogenesis. © 2018 Elsevier Inc

Off Label Use of Teriparatide in Spine

Teriparatide belongs to osteo-anabolic compounds and has been used in recent years to treat patients with osteoporosis, with the benefits of increased bone density. Its osteo-anabolic action has led to the investigation of the use of teriparatide for the improvement of bone quality. Apart from the enhancement of fracture union, teriparatide has been extensively studied in the promotion of fusion rate after spinal fusion. This study summarizes the preclinical and clinical results of the off-label use of teriparatide in the spine, and specifically its intermittent administration after instrumented spinal arthrodesis along with its impact on the spinal bone quality and spinal bone mineral density

Nerve injuries in total hip arthroplasty with a mini invasive anterior approach

Minimal invasive techniques in total hip arthroplasty (THA) have become increasingly popular during recent years. Despite much debate over the outcome of several minimal invasive techniques, complications arising from the use of anterior minimally invasive surgery (AMIS) for THA on a traction table are not well documented. Our study aims to focus on nerve damage during the AMIS procedure and the possible explanations of these injuries

Inducible nitric oxide synthase as a target for osteoarthritis treatment

Introduction: Inducible nitric oxide synthase (iNOS) is the enzyme responsible for the production of nitric oxide (NO), a major proinflammatory and destructive mediator in osteoarthritis (OA). Areas covered: This is a comprehensive review of the recent literature on the involvement of iNOS in osteoarthritis and its potential to be used as a target for OA treatment. Evidence from in vitro, in vivo and human studies was systematically collected using medical search engines. Preclinical studies have focused on the effect of direct and indirect iNOS inhibitors in both animal and human tissues. Apart from direct inhibitors, common pharmacological agents, herbal and dietary medicines as well as hyperbaric oxygen, low level laser and low intensity pulsed ultrasound have been shown to exhibit a chondroprotective effect by inhibiting the expression of iNOS. Expert opinion: Data support the further investigation of iNOS inhibitors for the treatment of OA in human studies and clinical trials. Indirect iNOS inhibitors such as interleukin 1 inhibitors also need to be studied in greater detail. Finally, human studies need to be conducted on the herbal and dietary medicines and on the non-invasive, non-pharmacological treatments. © 2018 Informa UK Limited, trading as Taylor & Francis Group